Fibroblast Growth Factor-1 (FGF-1) for the Treatment of Coronary Heart Disease

Patients with chronic, stable angina with documented coronary artery disease are eligible for
the study.

Inclusion criteria

1. Sign an informed consent form.

2. Age ≥25 and ≤75 years, either gender, and any race.

3. At least a 3 month history of chronic, stable angina and is relieved by rest and/or
nitroglycerin.

4. Documented symptomatic CCS Angina Classification of III to IV despite use of optimal
medical therapy as noted in Inclusion Criterion 10.

5. Pattern of CHD (coronary pathology) where percutaneous interventional therapy and/or
CABG is not recommended by the treating cardiologist. This decision should have a
documented basis in either complicated vessel physiology and/or lack of suitable
target vessels for both PTCA and CABG, or past history of complications.

6. One/two/three vessel disease as evidenced either by an angiographic documentation of
advanced atherosclerotic narrowing of ≥60% of at least one major epicardial coronary
artery (right coronary artery [RCA], left circumflex [LCX], or LAD [or any of their
branches]), or of diffuse type of CHD as evidenced by the appearance on coronary
angiography of multiple stenoses, multiple atherosclerotic plaques, and/or peripheral
occlusion(s) of coronary vessel(s) with and without a history of MIs.

7. demonstrate a radionuclide or angiographically determined left ventricular ejection
fraction (LVEF) ≥30%.

8. Pre-operative proof of reversible ischemia.

9. No evidence of proliferative retinopathy or significant non-proliferative retinopathy.

10. must be on optimal medical therapy for at least 2 months prior to entering the study,
as documented by a medical history. This will include medical management, and subjects
must enter the study on at least one of the following medications: beta-blockers,
calcium entry blockers, ranolizine, or long-acting nitrates.

11. Exercise duration during the qualifying treadmill tests at Visit 1 and Visit 2 is ≥3
and ≤9 minutes on a modified Bruce protocol.

12. Exercise durations for the qualifying treadmill tests at Visits 1 and 2 must satisfy
at least one of the two following conditions: (a) they differ by less than or equal to
20% of the longer time; (b) they differ by less than or equal to 60 seconds. Subjects
whose ETTs at Visits 1 and 2 do not satisfy at least one of these two conditions are
allowed a third ETT, at the investigator's discretion, from 5 to 7 days after Visit 2.
If a third ETT is done, then when compared with the second ETT it must satisfy at
least one of the two conditions above.

13. For a treadmill test result to support inclusion it must terminate in the presence of
angina for either of the following reasons: (a) angina becomes too severe to continue
the test AND there must be a horizontal depression or downsloping ST-segment of at
least 1 mm measured 80 ms from the J point as subsequently established by the
Biomedical Systems central ECG lab, or (b) angina of any grade AND there must be a
horizontal depression or downsloping ST-segment measured 80 ms from the J point of 2
mm during exercise. The qualifying time for the treadmill test will then be the time
to a horizontal depression or downsloping ST-segment of 1 mm compared to the
pre-exercise ST segment as subsequently established by the Biomedical Systems central
ECG lab.

14. A forced vital capacity (FVC) of ≥30%.

15. A negative pregnancy test in women of childbearing potential at Screening.

16. Female subjects must be post-menopausal or sterilized, or if she is of childbearing
potential, she is not breast feeding, has no intention to become pregnant during the
course of the study, and is using contraceptive drugs or devices.

17. Negative cancer screening tests according to the American Cancer Society ([ACS]
Appendix 13.8).

18. Ability to complete the study in compliance with the protocol.

Exclusion criteria

1. History of undergoing a CABG, PTCA or TMR or evidence of an acute MI in the last 3
months.

2. Subjects with malignancies or a history of malignancies (with the exception of basal
cell carcinoma [BCC] of the skin) will be excluded from the study. Those subjects with
a history of BCC are eligible for enrollment, and will be monitored by a qualified
dermatologist every 8 weeks for a period of 6 months for evaluation of their skin
condition. Subjects with existing BCC will be excluded from the study.

3. Evidence of concurrent clinically significant infection (e.g. elevated white blood
cell [WBC] count >13,000 x 109/L, temperature >38.5°C), evidence of "common cold" or
"flu."

4. Concomitant other structural heart disease, such as moderate to severe heart valve
disease, congenital heart disease, etc. other than evidence of congestive heart
failure that is directly related to past ischemic events.

5. Left ventricular thrombus (mobile or mural-based) as evidenced by ventriculogram or
echocardiography.

6. Creatine kinase (CK) levels >3 x upper limit of normal (ULN).

7. Renal insufficiency requiring dialysis or laboratory evidence of a serum creatinine
>2.0 mg/dL.

8. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 x ULN.

9. History of coagulation disorders or abnormal prothrombin time (PT) or partial
thromboplastin time (PTT) >1.5 x ULN, thrombocytopenia (<100,000/µl), or ongoing
anticoagulant therapy (with the exception of aspirin, up to 85 mg/day).

10. History of blood cell diseases.

11. Poorly controlled insulin-dependent diabetes mellitus (HbA1c >8%)

12. Pre-existing retinal disease, including proliferative retinopathy, severe
nonproliferative retinopathy.

13. Use of any illicit recreational drugs within the past year.

14. A positive test result for human immunodeficiency virus (HIV) antibody.

15. Screening ECG results demonstrating recent evidence of transmural ischemia.

16. Clinically significant ECG abnormalities, e.g.: QRS duration >0.12 seconds; QTc >450
ms in males or >460 ms in females;High-grade trioventricular (AV) block; Left bundle
branch block(LBBB; Left ventricular hypertrophy(LVH) with secondary ST-T changes;
Frequent, recurrent, or sustained ventricular arrhythmia; Resting ST segment
depression >1 mm (measured 80 ms beyond the J point) at baseline.

17. Subjects having a concomitant life-threatening disease in which their life expectancy
is estimated to be less than 2 years.

18. Any condition which in the opinion of the investigator would interfere with the
participant's ability to provide informed consent and comply with study instructions,
possibly confound interpretation of study results, or endanger the participant if he
took part in the trial.

19. Use of an investigational drug, device or product, or participation in a drug research
study within a period of 30 days prior to receiving IMP.

20. Any subject with unstable angina.

21. Heart failure New York Heart Association (NYHA) Functional Class III or IV.

22. Uncontrolled hypertension precluding exercise testing and/or contributing to angina
severity (systolic blood pressure [SBP] >200 mmHg or diastolic blood pressure [DBP]
>110 mmHg), or significant hypotension (SBP <90 mmHg or DBP <60 mmHg).

23. Subjects currently on External Counter Pulsation therapy or who have received this
therapy within 3 months prior to the screening date.

24. Any mobility or pulmonary complication that impedes the subject's ability to perform
an exercise stress test.

25. Total fasting serum cholesterol >200 mg/dL (if levels greater than or equal to 200
mg/dL, additional medical interventions can be initiated to bring levels below 200
mg/dL).

26. History of heparin-induced thrombocytopenia.

27. Subjects with a history of recurrent symptomatic atrial fibrillation or significant
ventricular arrhythmias.

28. Aortic or mitral valve replacement.

29. Subjects who have undergone heart transplantation.

30. Medical history and physical examination displaying any evidence that catheterization
is contraindicated.